Identification of Dlk1-Dio3 Imprinted Gene Cluster Noncoding RNAs as Novel Candidate Biomarkers for Liver Tumor Promotion | Zendy

Harri Lempiäinen | Zendy; Philippe Couttet | Zendy; Federico Bolognani | Zendy; Arne Müller | Zendy; Valérie Dubost | Zendy; Raphaëlle Luisier | Zendy; Alberto del Rio-Espinola | Zendy; Veronique Vitry | Zendy; Elif B. Unterberger | Zendy; John P. Thomson | Zendy; Fridolin Treindl | Zendy; Ute Metzger | Zendy; Clemens Wrzodek | Zendy; Florian Hahne | Zendy; Tulipan Zollinger | Zendy; Sarah Brasa | Zendy; Magdalena Kalteis | Zendy; M. Marcellin | Zendy; Fanny Giudicelli | Zendy; Albert Braeuning | Zendy; Laurent Morawiec | Zendy; Natasa Zamurovic | Zendy; Ulrich Längle | Zendy; Nico Scheer | Zendy; Dirk Schübeler | Zendy; Jay I. Goodman | Zendy; Salah-Dine Chibout | Zendy; Jennifer Marlowe | Zendy; Diethilde Theil | Zendy; David J. Heard | Zendy; Olivier Grenet | Zendy; Andreas Zell | Zendy; Markus F. Templin | Zendy; Richard R. Meehan | Zendy; C. Roland Wolf | Zendy; Clifford R. Elcombe | Zendy; Michael Schwarz | Zendy; Pierre Moulin | Zendy; Rémi Terranova | Zendy; Jonathan G. Moggs | Zendy

Open Access

Identification of Dlk1-Dio3 Imprinted Gene Cluster Noncoding RNAs as Novel Candidate Biomarkers for Liver Tumor Promotion

Author(s) -

Harri Lempiäinen,

Philippe Couttet,

Federico Bolognani,

Arne Müller,

Valérie Dubost,

Raphaëlle Luisier,

Alberto del Rio-Espinola,

Veronique Vitry,

Elif B. Unterberger,

John P. Thomson,

Fridolin Treindl,

Ute Metzger,

Clemens Wrzodek,

Florian Hahne,

Tulipan Zollinger,

Sarah Brasa,

Magdalena Kalteis,

M. Marcellin,

Fanny Giudicelli,

Albert Braeuning,

Laurent Morawiec,

Natasa Zamurovic,

Ulrich Längle,

Nico Scheer,

Dirk Schübeler,

Jay I. Goodman,

Salah-Dine Chibout,

Jennifer Marlowe,

Diethilde Theil,

David J. Heard,

Olivier Grenet,

Andreas Zell,

Markus F. Templin,

Richard R. Meehan,

C. Roland Wolf,

Clifford R. Elcombe,

Michael Schwarz,

Pierre Moulin,

Rémi Terranova,

Jonathan G. Moggs

Publication year - 2012

Publication title -

toxicological sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.352

H-Index - 183

eISSN - 1096-6080

pISSN - 1096-0929

DOI - 10.1093/toxsci/kfs303

Subject(s) - meg3 , biology , epigenetics , gene expression , microrna , cancer research , gene , carcinogenesis , genetics , rna , long non coding rna

The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, suggesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.

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